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Host candidate gene polymorphisms and clearance of drug-resistant Plasmodium falciparum parasites

BACKGROUND: Resistance to anti-malarial drugs is a widespread problem for control programmes for this devastating disease. Molecular tests are available for many anti-malarial drugs and are useful tools for the surveillance of drug resistance. However, the correlation of treatment outcome and molecu...

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Autores principales: Diakite, Mahamadou, Achidi, Eric A, Achonduh, Olivia, Craik, Rachel, Djimde, Abdoulaye A, Evehe, Marie-Solange B, Green, Angie, Hubbart, Christina, Ibrahim, Muntasir, Jeffreys, Anna, Khan, Baldip K, Kimani, Francis, Kwiatkowski, Dominic P, Mbacham, Wilfred F, Jezan, Sabah Omar, Ouedraogo, Jean Bosco, Rockett, Kirk, Rowlands, Kate, Tagelsir, Nawal, Tekete, Mamadou M, Zongo, Issaka, Ranford-Cartwright, Lisa C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3177816/
https://www.ncbi.nlm.nih.gov/pubmed/21867552
http://dx.doi.org/10.1186/1475-2875-10-250
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author Diakite, Mahamadou
Achidi, Eric A
Achonduh, Olivia
Craik, Rachel
Djimde, Abdoulaye A
Evehe, Marie-Solange B
Green, Angie
Hubbart, Christina
Ibrahim, Muntasir
Jeffreys, Anna
Khan, Baldip K
Kimani, Francis
Kwiatkowski, Dominic P
Mbacham, Wilfred F
Jezan, Sabah Omar
Ouedraogo, Jean Bosco
Rockett, Kirk
Rowlands, Kate
Tagelsir, Nawal
Tekete, Mamadou M
Zongo, Issaka
Ranford-Cartwright, Lisa C
author_facet Diakite, Mahamadou
Achidi, Eric A
Achonduh, Olivia
Craik, Rachel
Djimde, Abdoulaye A
Evehe, Marie-Solange B
Green, Angie
Hubbart, Christina
Ibrahim, Muntasir
Jeffreys, Anna
Khan, Baldip K
Kimani, Francis
Kwiatkowski, Dominic P
Mbacham, Wilfred F
Jezan, Sabah Omar
Ouedraogo, Jean Bosco
Rockett, Kirk
Rowlands, Kate
Tagelsir, Nawal
Tekete, Mamadou M
Zongo, Issaka
Ranford-Cartwright, Lisa C
author_sort Diakite, Mahamadou
collection PubMed
description BACKGROUND: Resistance to anti-malarial drugs is a widespread problem for control programmes for this devastating disease. Molecular tests are available for many anti-malarial drugs and are useful tools for the surveillance of drug resistance. However, the correlation of treatment outcome and molecular tests with particular parasite markers is not perfect, due in part to individuals who are able to clear genotypically drug-resistant parasites. This study aimed to identify molecular markers in the human genome that correlate with the clearance of malaria parasites after drug treatment, despite the drug resistance profile of the protozoan as predicted by molecular approaches. METHODS: 3721 samples from five African countries, which were known to contain genotypically drug resistant parasites, were analysed. These parasites were collected from patients who subsequently failed to clear their infection following drug treatment, as expected, but also from patients who successfully cleared their infections with drug-resistant parasites. 67 human polymorphisms (SNPs) on 17 chromosomes were analysed using Sequenom's mass spectrometry iPLEX gold platform, to identify regions of the human genome, which contribute to enhanced clearance of drug resistant parasites. RESULTS: An analysis of all data from the five countries revealed significant associations between the phenotype of ability to clear drug-resistant Plasmodium falciparum infection and human immune response loci common to all populations. Overall, three SNPs showed a significant association with clearance of drug-resistant parasites with odds ratios of 0.76 for SNP rs2706384 (95% CI 0.71-0.92, P = 0.005), 0.66 for SNP rs1805015 (95% CI 0.45-0.97, P = 0.03), and 0.67 for SNP rs1128127 (95% CI 0.45-0.99, P = 0.05), after adjustment for possible confounding factors. The first two SNPs (rs2706384 and rs1805015) are within loci involved in pro-inflammatory (interferon-gamma) and anti-inflammatory (IL-4) cytokine responses. The third locus encodes a protein involved in the degradation of misfolded proteins within the endoplasmic reticulum, and its role, if any, in the clearance phenotype is unclear. CONCLUSIONS: The study showed significant association of three loci in the human genome with the ability of parasite to clear drug-resistant P. falciparum in samples taken from five countries distributed across sub-Saharan Africa. Both SNP rs2706384 and SNP1805015 have previously been reported to be associated with risk of malaria infection in African populations. The loci are involved in the Th1/Th2 balance, and the association of SNPs within these genes suggests a key role for antibody in the clearance of drug-resistant parasites. It is possible that patients able to clear drug-resistant infections have an enhanced ability to control parasite growth.
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spelling pubmed-31778162011-09-22 Host candidate gene polymorphisms and clearance of drug-resistant Plasmodium falciparum parasites Diakite, Mahamadou Achidi, Eric A Achonduh, Olivia Craik, Rachel Djimde, Abdoulaye A Evehe, Marie-Solange B Green, Angie Hubbart, Christina Ibrahim, Muntasir Jeffreys, Anna Khan, Baldip K Kimani, Francis Kwiatkowski, Dominic P Mbacham, Wilfred F Jezan, Sabah Omar Ouedraogo, Jean Bosco Rockett, Kirk Rowlands, Kate Tagelsir, Nawal Tekete, Mamadou M Zongo, Issaka Ranford-Cartwright, Lisa C Malar J Research BACKGROUND: Resistance to anti-malarial drugs is a widespread problem for control programmes for this devastating disease. Molecular tests are available for many anti-malarial drugs and are useful tools for the surveillance of drug resistance. However, the correlation of treatment outcome and molecular tests with particular parasite markers is not perfect, due in part to individuals who are able to clear genotypically drug-resistant parasites. This study aimed to identify molecular markers in the human genome that correlate with the clearance of malaria parasites after drug treatment, despite the drug resistance profile of the protozoan as predicted by molecular approaches. METHODS: 3721 samples from five African countries, which were known to contain genotypically drug resistant parasites, were analysed. These parasites were collected from patients who subsequently failed to clear their infection following drug treatment, as expected, but also from patients who successfully cleared their infections with drug-resistant parasites. 67 human polymorphisms (SNPs) on 17 chromosomes were analysed using Sequenom's mass spectrometry iPLEX gold platform, to identify regions of the human genome, which contribute to enhanced clearance of drug resistant parasites. RESULTS: An analysis of all data from the five countries revealed significant associations between the phenotype of ability to clear drug-resistant Plasmodium falciparum infection and human immune response loci common to all populations. Overall, three SNPs showed a significant association with clearance of drug-resistant parasites with odds ratios of 0.76 for SNP rs2706384 (95% CI 0.71-0.92, P = 0.005), 0.66 for SNP rs1805015 (95% CI 0.45-0.97, P = 0.03), and 0.67 for SNP rs1128127 (95% CI 0.45-0.99, P = 0.05), after adjustment for possible confounding factors. The first two SNPs (rs2706384 and rs1805015) are within loci involved in pro-inflammatory (interferon-gamma) and anti-inflammatory (IL-4) cytokine responses. The third locus encodes a protein involved in the degradation of misfolded proteins within the endoplasmic reticulum, and its role, if any, in the clearance phenotype is unclear. CONCLUSIONS: The study showed significant association of three loci in the human genome with the ability of parasite to clear drug-resistant P. falciparum in samples taken from five countries distributed across sub-Saharan Africa. Both SNP rs2706384 and SNP1805015 have previously been reported to be associated with risk of malaria infection in African populations. The loci are involved in the Th1/Th2 balance, and the association of SNPs within these genes suggests a key role for antibody in the clearance of drug-resistant parasites. It is possible that patients able to clear drug-resistant infections have an enhanced ability to control parasite growth. BioMed Central 2011-08-25 /pmc/articles/PMC3177816/ /pubmed/21867552 http://dx.doi.org/10.1186/1475-2875-10-250 Text en Copyright ©2011 Diakite et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Diakite, Mahamadou
Achidi, Eric A
Achonduh, Olivia
Craik, Rachel
Djimde, Abdoulaye A
Evehe, Marie-Solange B
Green, Angie
Hubbart, Christina
Ibrahim, Muntasir
Jeffreys, Anna
Khan, Baldip K
Kimani, Francis
Kwiatkowski, Dominic P
Mbacham, Wilfred F
Jezan, Sabah Omar
Ouedraogo, Jean Bosco
Rockett, Kirk
Rowlands, Kate
Tagelsir, Nawal
Tekete, Mamadou M
Zongo, Issaka
Ranford-Cartwright, Lisa C
Host candidate gene polymorphisms and clearance of drug-resistant Plasmodium falciparum parasites
title Host candidate gene polymorphisms and clearance of drug-resistant Plasmodium falciparum parasites
title_full Host candidate gene polymorphisms and clearance of drug-resistant Plasmodium falciparum parasites
title_fullStr Host candidate gene polymorphisms and clearance of drug-resistant Plasmodium falciparum parasites
title_full_unstemmed Host candidate gene polymorphisms and clearance of drug-resistant Plasmodium falciparum parasites
title_short Host candidate gene polymorphisms and clearance of drug-resistant Plasmodium falciparum parasites
title_sort host candidate gene polymorphisms and clearance of drug-resistant plasmodium falciparum parasites
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3177816/
https://www.ncbi.nlm.nih.gov/pubmed/21867552
http://dx.doi.org/10.1186/1475-2875-10-250
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